As an antigen protein and an enzyme, prostate-specific membrane antigen (PSMA) is now recognized as an important target for the development of imaging and therapeutic agents. PSMA PET/CT utilizes radiographic tracers targeting the PSMA protein expressed on the surface of prostate cancer cells to identify foci of disease that may not be visible on conventional staging imaging modalities. Two PSMA-based imaging agents have already been approved by the US Food and Drug Administration (FDA) for PET imaging of PSMA-positive lesions in men with prostate cancer.1,2 Gallium Ga 68 gozetotide (gallium GA-68 PSMA-11) ) and piflufolastat F 18 (18F-DCFPyL) are both indicated for patients with suspected metastasis who are eligible for initial definitive therapy and for patients with suspected recurrence based on an elevated PSA level.
In the application of PSMA to targeted radioligand therapy (theranostics), a significant life-prolonging effect was demonstrated in the VISION trial when the beta-particle emitter lutetium-177 (177Lu)-PSMA-617 was added to standard care in patients with progressive metastatic castration-resistant prostate cancer (mCRPC) after at least one taxane-based chemotherapy regimen and an androgen-receptor pathway inhibitor.3 Based on the VISION trial results, the FDA granted Priority Review for 177Lu-PSMA-617.4 Meantime, numerous clinical trials are ongoing with other PSMA-targeted imaging and therapeutic agents.
In a conversation with GU Oncology Now editor, Catherine H. Marshall, MD, MPH, Assistant Professor in the Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, spoke about how PSMA PET is impacting real world clinical practice in the diagnosis and management of prostate cancer. The first part of the conversation was published in January 2022, and in the second part (below), Dr Marshall expands on her views on the use of PSMA PET/CT.
GU Oncology Now: Last time we spoke about how you use PSMA PET/CT in your own practice. Today, could you tell us what improvements you think PSMA-based diagnosis provides in prostate cancer management, in either the newly diagnosed patient, the patient with biochemical recurrence, or the patient with metastatic castration-resistant disease (CRPC).
Dr Marshall: I think right now, where PSMA PET/CT provides the most improvement for newly diagnosed prostate cancer and biochemical recurrent disease, is in identifying the location of the disease. This is particularly important in these two settings because treatments are localized in these cases. So, for example, in newly diagnosed disease, if you’re thinking about doing radiation or surgery, and you know ahead of time that there’s extensive disease outside that area, that would be something important to know. So it helps with localizing the disease, especially when a localized treatment is being considered. With CRPC right now, it’s mainly used to help determine whether a patient is going to benefit from PSMA-based treatment.
GU Oncology Now: What about the newly diagnosed patient, in whom we would usually obtain imaging prior to any therapeutic intervention, radiation, or surgery? How does PSMA-based imaging compare with other imaging modalities like MRI in that setting?
Dr Marshall: One helpful study for this was the proPSMA trial, published in 2020, 5 which looked at PSMA PET/CT in patients with high-risk prostate cancer before curative- intent surgery or radiotherapy. It showed a 27% greater accuracy of detecting disease with PSMA PET/CT than with conventional imaging, and also showed that PSMA-based imaging had higher sensitivity and specificity. So, it is certainly better. I don’t think it’s going to totally replace MRIs in newly diagnosed prostate cancer, but I think it will probably end up being used in conjunction with MRI for localized disease.
GU Oncology Now: Do you think that prostate cancer management guidelines will recommend PSMA PET/CT imaging in high-risk patients at some point, or is it still too early for that?
Dr Marshall: I believe that at some point, it will almost certainly be added to the guidelines. At present, we’re still learning exactly how to use it and how we should change clinical management based on the results that we get from PSMA scans. But I believe that its use and our knowledge about it will only increase in the future.
GU Oncology Now: In terms of actual staging results, do you know of any differences between the type of information an MRI can provide versus PSMA PET/CT?
Dr Marshall: For disease in the prostate and for pelvic disease, MRI is still going to be useful. But then, certainly for disease outside of the prostate, and the MRI imaging field, PSMA PET is obviously going to be better.
GU Oncology Now: Do you think there will be a role for PSMA PET imaging in patients with non-metastatic CRPC? Will it identify patients with occult metastatic disease that isn’t being picked up on conventional imaging? Do you think it will result in any upstaging of these patients?
Dr Marshall: If we define metastatic disease as disease detected based on imaging outside of the pelvis, then PSMA scans will certainly increase the number of patients who have metastatic disease by that criterion. The question that I think we are still trying to figure out the answer to is how that should change treatment and whether it should change treatment in everybody. I see a lot of patients with biochemical recurrence. For people with a rising PSA level, let’s say after radical prostatectomy, a standard option would be salvage radiation therapy. Now, if somebody had a PSMA scan that showed extensive disease outside of the pelvis, then it makes sense that salvage radiation to the prostate bed might not benefit that person. However, it’s not entirely clear whether upstaging all those patients and then treating them the same way you would someone with metastatic disease that’s been detected on conventional scans, would have the same outcomes.
GU Oncology Now: So basically, we need more data to guide us in this setting
Dr Marshall: Yes, that’s almost always the answer, especially in this setting. We already have a lot more information, but we don’t necessarily know how best to use all of it right now.
Akhil Abraham Saji, MD is a urology resident at New York Medical College / Westchester Medical Center. His interests include urology education and machine learning applications in urologic care. He is a founding and current member of the EMPIRE Urology New York AUA section team.
References
- FDA approves first PSMA-targeted PET imaging drug for men with prostate cancer. Press release. FDA. December 1, 2020. Accessed January 30, 2022. https://www.fda.gov/news-events/press-announcements/fda-approves-first-psma-targeted-pet-imaging-drug-men-prostate-cancer
- FDA approves second PSMA-targeted PET imaging drug for men with prostate cancer. FDA. May 27, 2021. Accessed January 30, 2022. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-second-psma-targeted-pet-imaging-drug-men-prostate-cancer
- Sartor O, de Bono J, Chi KN, et al; VISION Investigators. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091-1103. DOI: 1056/NEJMoa2107322
- FDA grants Priority Review for investigational targeted radioligand therapy 177Lu-PSMA-617 for patients with metastatic castration-resistant prostate cancer (mCRPC). Novartis. September 28, 2021. Accessed January 30, 2022. https://www.novartis.com/news/fda-grants-priority-review-investigational-targeted-radioligand-therapy-177lu-psma-617-patients-metastatic-castration-resistant-prostate-cancer-mcrpc
- Hofman MS, Lawrentschuk N, Francis RJ, et al ; proPSMA Study Group Collaborators. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. Lancet. 2020;395(10231):1208-1216. DOI: 1016/s0140-6736(20)30314-7
